Bone metastasis is one of the most common causes of pain in cancer patients. In the United States, it is estimated that of 1.4 million patients who will be diagnosed with cancer, 30% to 70% will develop skeletal metastases. In one study, the prevalence of pain was shown to be 55% of ambulatory patients, and 46% of those patients reporting pain received inadequate analgesics. Each year there is estimated 150,000 painful bone metastases cases from advanced lung, breast, and prostate cancer in the United States.
Bone cancer is a growth found in any part of the bone. Most bone cancers develop predominantly from bone, cartilage, muscle, fibrous tissue, fatty tissue or nerve tissue. Primary bone cancer originates in the bone itself. The most common primary malignancies that metastasize to the bone are breast, kidney, lung, and prostate. The most common sites of metastasis are the vertebrae, pelvis, and long bones. Secondary bone cancers, which are more common than primary cancers, spread from other cancerous cells in the body. Primary and Secondary types of bone cancer are described below.
Primary Bone Cancer:    A. Osteosarcome: the most common type of primary bone cancer, develops in new tissues of growing bones, particularly the knees, upper legs, upper arms. Patients often children and young people between 10 and 25 years old.    B. Ewing's Sarcoma: this sarcoma begins in immature nerve tissue in the bone marrow of the body's large bones, i.e. pelvis, upper legs, ribs and arms. Ewing's sarcoma affects children and young adults.    C. Chondrosarcoma: this usually arises in the cartilage, soft connective tissue of the pelvis, upper legs and shoulders. This type of malignancy most frequently affects adults over 50 years old.
Secondary Bone Caner:    It is more common than primary bone cancer and usually occurs later in life. Cancers that tend to spread rapid to bone are breast, lung, prostate, thyroid, and kidney. Pain usually results when a tumor pushes on bones, nerves, or other organs in the body.
Current pain control treatments include:    A. Surgery to remove all or part of the affected bone.    B. Chemotherapy involves the use of drugs that target the given tumor cells. Significant side effects are problematic.    C. Radiation Therapy utilizes X-ray or other radioactive source to destroy the development of abnormal cells. Similar to chemotherapy, radiation may impact normal tissues.    D. Hormone Therapy is used to stem secondary bone cancers of the prostate and breast.    E. Analgesic Drugs: radiopharmaceuticals, bisphosphonates, calcitonin and others to treat pain via blocking pain pathways or inhibit local growth factors.    F. Radiofreqency ablation on benign lesion of bone (osteoid osteoma) targeting at nidus, where composed of a variably calcified meshwork of bony trabeculae on a background of fibrous, vascular, and nerve tissue. Percutaneous RF ablation treats the margin of the lesion at the soft-tissue-bone interface for pain reduction.
The above therapies may have serious side effects and limitations can include:    A. Poor therapeutic response or toxicity from chemotherapy.    B. Intolerable analgesic related side effects may develop with increasing analgesic doses.    C. Limited patients are suitable for radiation therapy because of radiation insensitivity of the neoplasm or limitations of radiation dose that can cause damage to normal structure and healthy cells.
Although terminal patients undergo combinational treatment plan, the current treatments are ineffective to relieve pain.
Tumor metastasis to bone is associated with bone destruction and new bone formation. Bone pain often results from the tumor impinging on nerve tissue, disrupting normal bone remodeling process, and displacing bone. The pain is usually described as a deep, aching over the site of the involved bone.
The sensory receptors within the human body are sensitive to tissue damaging or stimuli that are prevalent in skin, muscle, joint, bone and other connective tissues. Those nociceptors (sensory receptors) are sensitive to response to mechanical, thermal, and chemical cutaneous stimuli. It is believed that nociceptor sensitization is a physiologic mechanism of persistent pain. Once nociceptors activated locally, it transduces chemical, mechanical, or thermal stimuli into afferent impulses that enter the nervous system to the brain for pain perception. Particularly, A-δ mechanoreceptors and C-nociceptors appear to be localized to connective tissue between muscle fibers and in blood vessel walls or tendons, and in the joint capsule and periosteum.
Particularly, numerous studies have shown that the periosteum, which is comprised of fibrous connective tissue sheath that covers the external surface of all bones, is densely innervated by both sensory and sympathetic fibers. Nerves are distributed to the Periosteum and accompany the nutrient arteries into the interior of the bone. Fine nerve endings are found in bone marrow, periosteum, cortex, and associated muscles and ligaments. The prevailing opinion is that bone pain arises predominantly from the densely innervated periosteum, where is the area of interest for ablating local pain receptors utilizing ultrasound to reduce bone pain.